Hydroxylation of the eukaryotic ribosomal decoding center affects translational accuracy
Loenarz C., Sekirnik R., Thalhammer A., Ge W., Spivakovsky E., Mackeen MM., McDonough MA., Cockman ME., Kessler BM., Ratcliffe PJ., Wolf A., Schofield CJ.
Significance The processing of DNA sequences into proteins is fine-tuned to meet the conflicting demands of accuracy and speed. DNA mutations can introduce premature stop codons, leading to inactive proteins. We report that oxygen-dependent posttranslational modification of the ribosomal decoding center affects stop codon readthrough in an mRNA sequence-dependent manner. Our work demonstrates that oxygenases catalyzing RPS23 hydroxylation are conserved in eukaryotes, including yeasts, flies, and humans. In basal eukaryotes, RPS23 undergoes two hydroxylations, whereas in animals we only observe one hydroxylation. Yeast ribosomes lacking hydroxylation manifest altered stop codon readthrough up to ∼10-fold. The results reveal oxygen-dependent modifications that regulate translational accuracy and suggest unprecedented approaches to modulating ribosomal accuracy for medicinal application.